title: Doxycycline reduces mortality to lethal endotoxemia by reducing nitric oxide synthesis via an interleukin-10-independent mechanism.
abstract: It was demonstrated that doxycycline protected BALB/c mice injected intraperitoneally with bacterial lipopolysaccharide (LPS) against lethal septic shock. Doxycycline (at 1.5 mg/kg) exerted its protective effect by inhibiting nitrate production by an interleukin-10-independent mechanism. Experiments carried out in vitro also indicated that doxycycline inhibited NO synthesis by LPS-activated macrophages without inducing any significant modification in interleukin-10 release. These data suggest that the direct inhibition of nitrate release is the main mechanism of the antiinflammatory activity of doxycycline in septic shock.
authors.affiliation: Institute of General Pathology, University of Palermo, Italy.
authors.forename: P
authors.initials: P
authors.lastname: D'Agostino
authors.forename: M
authors.initials: M
authors.lastname: La Rosa
authors.forename: C
authors.initials: C
authors.lastname: Barbera
authors.forename: F
authors.initials: F
authors.lastname: Arcoleo
authors.forename: G
authors.initials: G
authors.lastname: Di Bella
authors.forename: S
authors.initials: S
authors.lastname: Milano
authors.forename: E
authors.initials: E
authors.lastname: Cillari
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004318:Doxycycline / Q000008:administration & dosage / Q000627:therapeutic use*; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D012772:Shock, Septic / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D009566:Nitrates; D016753:Interleukin-10; D009569:Nitric Oxide; D004318:Doxycycline